J Chin Med 6(1):1-12, 1995

ANTITUMOR EFFECTS OF GANODERMA LUCIDUM

Shiuh-Sheng Lee, Yau-Huei Wei, Chieh-Fu Chen, Sheng-Yuan Wang and
Kuang-Yao Chen
Department of Biochemistry, National Yang-Ming University,
National Research Institute of Chinese Medicine,
Department of Medical Research and Cancer Therapy Center, Veterans General Hospital-Taipei, Taipei, Taiwan
（Received 14th October 1994, revised MS received 23rd January 1995, accepted 25th January 1995）

Ganoderma lucidum has been established to be an autitumor natural product. The hot water extracts of mycelium of G.. lucidum(GLP) exhibited antitumor effect against fibrosarcoma in male and female C3H mice and inhibited the metastasis of the lung. Moreover, we have fractionated GLP into polysaccharide fraction [GLP(AI)] and non- polysaccharide fraction. We found that GLP(AI) is the major component to show the in vivo antitumor effect on fibrosarcoma growth in C3H mice. The effects of GLP(AI) on cytotoxic activity of splenic natural killer cells(NK) were assessed in normal mice and in tumor bearing mice. The results show that either intravenous, intraperitoneal or oral administration of GLP(AI) produced a does-related increase in the splenic NK activity in different mouse strains. In addition, administration of GLP(AI) produced an increase in the titer of serum interferon (IFN). Furthermore, the decreased splenic NK cytotoxicity of tumor-bearing mice was restored by GLP(AI) treatment. The effect of GLP(AI) on the induction of differentiation in leukemic U937 cells was also examined. We found that it could stimulate blood mononuclear cells to secrete cytokines which were both anti-proliferative and differentiation inductive to the leukemic U937 cells.
Furthermore, antitumor activity of G. lucidum on intraperitoneally implanted Lewis lung carcinoma in synergenic C57BL/6 mice was investigated. The results showed that GLP significantly increased the life-span of tumor-implanted mice, when administered intraperitoneally alone or in combination with cytotoxic antitumor drugs (adriamycin, fluorouracil, thioguanine, methotrexate, cisplation) or synthetic immunomodulator (imexon). The GLP was not cytotoxic to cultured cells and the antitumor activity was abolished by pretreatment of mice with cyclosporine. The active principle(s) was found to be present predominantly in the GLP(AI) fraction.
Key Words: Ganoderma lucidum, polysaccharide, Natural killer cell, Cytokine, Differentiation, Immunomodulator.